MRI identifies dense, permeable vasculature associated with angiogenesis in malignant tumors based on uptake of contrast agents. However, increases in the accuracy of MRI are needed. Improving detection of angiogenesis by MRI would have a significant impact on detection and treatment of cancer. Previous work in this laboratory showed that high spectral and spatial resolution (HiSS) MRI increases sensitivity to the effects of contrast agents because it detects spectrally inhomogeneous affects of contrast agents (CA's). CA effects on small components of the water resonance from single small voxels may indicate the presence of sub-voxelar angiogenic foci. The proposed research tests the hypothesis that contrast enhanced HiSS MRI has increased sensitivity and specificity for detection of ang/ogenes/s. We will develop methods for acquiring and processing HiSS datasets to maximize sensitivity to contrast media and evaluate whether HiSS MRI accurately detects angiogenesis. HiSS MRI measurements of blood volume, capillary permeability, and vascular architecture in very small voxels will be evaluated. Sensitivity of HiSS MRI to vascular structure and function will be compared to that of high-resolution conventional MRI. To develop and evaluate HiSS detection of tumor vasculature we will: 1. Improve methods for acquiring and processing HiSS data that optimize sensitivity to contrast agents. 2. Measure vascular volume and permeability using HiSS imaging of high molecular weight CA's. 3. Compare HiSS data with conventional high-resolution MRI methods. 4. Compare HiSS image data to histological measurements of micro-vessel density and vascular casts. 5. Test the ability of HiSS to detect effects of anti-angiogenic therapy on tumor vasculature. This proposal requests support for development of innovative MR methods that attack an important clinical problem. The areas of innovation are 1) HiSS is a new approach to MRI 2) HiSS detection of effects of contrast agents is a novel approach to dynamic contrast enhanced MRI. HiSS MR data are currently acquired in clinically acceptable run-times on whole-body scanners using echo-planar-spectroscopic imaging (EPSI). Thus, the results of the proposed work could be rapidly translated to clinical practice and would improve patient care.